PROJECT SUMMARY/ABSTRACT Cerebral microbleeds (CMBs) are a common cerebrovascular pathology found with aging. Even though CMBs are a proven risk factor for intracerebral hemorrhage, there is little data to guide clinicians and patients regarding the risk of future hemorrhage with incidentally identified CMBs. This leads to clinical dilemmas for individuals who require antithrombotic medications to prevent cerebral or cardiac ischemia but also have a CMB predisposing them to hemorrhage. In particular, prior studies of CMBs have not been population-based or have not included amyloid- and tau-positron emission tomography (PET). The primary objective of this grant is to determine the clinical outcome of individuals with CMBs in a population-based setting with multimodal neuroimaging. After determining the prevalence and incidence of CMBs, we will determine the risk of future intracerebral hemorrhage among individuals with CMBs by harnessing outcome data from the Rochester Epidemiology Project. The secondary objective of the grant is to determine the pathophysiologic and pathologic basis for CMBs. We will determine which neuroimaging biomarkers (amyloid PET, tau PET, white- matter hyperintensity, lacunar stroke) are associated with CMBs by location and predict the development of CMBs. Lastly, we will identify individuals with CMBs, who come to autopsy, by antemortem magnetic resonance imaging. By sampling the region of CMB, we will determine the pathologic background of CMBs. We will capitalize on the existing population-based and prospective Mayo Clinic Study of Aging (MCSA) cohort. The population-based nature of the MCSA sample is ideally suited for the development and generalizability of the findings because it captures incidentally detected CMBs. One of the strengths of the proposal is to inform clinical decision-making for the large number of elderly individuals with CMBs. This project will serve as a career development award for the Principal Investigator. During the project, the PI will receive hands-on experience and develop expertise in neuroimaging analysis and quantification, and neuropathology. In addition, the PI will receive mentorship from experienced investigators in aging and CMBs, and take courses on leadership development.